Stochasticity plays an important role in many biological processes. Examples include bistable genetic switches, noise enhanced robustness of oscillations, and uctuation enhanced sensitivity or stochastic focusing. Numerous cellular systems, including development, morphogenesis, polarization and chemotaxis rely on spatial stochastic noise for robust performance. At the same time, stochastic simulations are complex and consume large amounts of computer time. They may require the researcher to be procient in the use of one or more complex software packages. Learning to use existing simulation tools and to integrate them with other software takes considerable time. In many cases, the tools do not exist and require the expertise of mathematicians and computer scientists to develop them. Often, researchers must purchase and maintain clusters of computers to perform the large-scale computations. All of this adds costs and delays to the research process. Currently, there exists no software package that allows researchers to easily build a stochastic model of a biological system, and scale it up to increasing levels of detail and complexity. We propose to build an environment where the modeler can focus his/her attention on the biology; alleviating the burden of software installation and versions, mathematical algorithms, code optimizations, computer systems, etc. This environment will run on laptops and computer workstations (for small problems), extending on demand to high-performance compute clusters, grids, and public or private clouds; thus creating a cost-eective and energy-ecient solution for simulations of all sizes. We will equip this environment with state of the art software for key classes of problems, and make it easy for software developers to integrate new and improved algorithms without the need to develop their own software infrastructure. We will develop new algorithms and software to address key computational capabilities that have not previously been attainable: (1) fully- adaptive, hybrid solvers for sti (and nonsti) well-mixed systems (2) ecient computation of probabilities of rare events, and (3) simulation of spatial stochastic systems at speeds that are several orders of magnitude faster than previous methods. The availability of such a community resource will enable and accelerate progress in both biology and algorithm development. PUBLIC HEALTH RELEVANCE: Relevance Computer modeling and simulation provide critical insights necessary for the understanding of fundamental cellular systems: researchers postulate a mathematical model incorporating the relationships between key components, simulate it on a computer, and then compare the results to experiment to determine whether the model is plausible. Such an understanding, or model, of a biochemical process is important for drug targeting and therapeutic intervention. Stochasticity (randomness) plays an important role in many biological processes. Such simulations are complex and consume large amounts of computer time. We propose to build a comprehensive, state of the art software system for simulating stochastic models. The availability of such a community resource will enable and accelerate progress in biology and medicine.